The plasma contact system as a modulator of innate immunity

Purpose of review The contact system is a plasma protease cascade, which activates the proinflammatory kallikrein–kinin system and the procoagulant intrinsic coagulation pathway. Recent advances demonstrating the novel functions of this system as a key player of innate immune system will be introduced in the present review. Recent findings The role of the contact system is to initiate and participate in pathophysiological responses to injury, mainly the processes of coagulation and inflammation. The past few years have seen substantial progress, showing a new role of this system in regulation of innate immunity. The relationship between high-molecular-weight kininogen and lipopolysaccharide (LPS) has been investigated and a new function of high-molecular-weight kininogen has been identified as the critical LPS carrier supporting endotoxemia. In contrast, the role of high-molecular-weight kininogen in Klebsiella pneumoniae sepsis is limited. Coagulation factor XII (FXII) plays a detrimental role in murine wound healing and host defense against K. pneumoniae sepsis. In the pathogenesis of arthritis and colitis, the activation of plasma kallikrein and downstream cleavage of high-molecular-weight kininogen and release of bradykinin constitutes a critical pathway in the innate immune mechanism, whereas FXII is not important. Summary Current findings indicate that the plasma contact system functions as an important constituent of innate immune system, contributing to ...
Source: Current Opinion in Hematology - Category: Hematology Tags: HEMOSTASIS AND THROMBOSIS: Edited by Alvin H. Schmaier Source Type: research

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IJERPH, Vol. 18, Pages 9655: Long-Term Sequelae of Frostbite—A Scoping Review International Journal of Environmental Research and Public Health doi: 10.3390/ijerph18189655 Authors: Ivo B. Regli Giacomo Strapazzon Marika Falla Rosmarie Oberhammer Hermann Brugger Frostbite is tissue damage caused by freezing temperatures and constitutes an important cause of morbidity in cold climate zones and high altitude. The direct effects of sub-zero temperatures lead to tissue freezing, electrolyte shifts and pH alterations, microvascular damage, and eventually to cell death. Upon rewarming, inflammatory reperfusi...
Source: International Journal of Environmental Research and Public Health - Category: Environmental Health Authors: Tags: Review Source Type: research
Purpose of review Janus Kinase (JAK) inhibitors have been successfully utilized in the clinical treatment of several rheumatologic (e.g. rheumatoid arthritis) and inflammatory diseases (e.g. hemophagocytic lymphohistiocytosis). Based on the growing evidence that moderate and severe COVID-19 infections are associated with a dysregulated inflammatory state, this class of medications has been repurposed as a potential therapy for COVID-19, an infection caused by Severe Acute Respiratory Syndrome Coronavirus 2. Recent findings Three JAK inhibitors have been evaluated in human studies of COVID-19: Baricitinib, Tofaci...
Source: Current Opinion in Critical Care - Category: Nursing Tags: SEVERE INFECTIONS: Edited by Andre C. Kalil Source Type: research
ObjectiveSomatic mutations inUBA1 cause a newly defined syndrome known as VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome). More than 50% of patients currently identified as having VEXAS met diagnostic criteria for relapsing polychondritis (RP), but clinical features that characterize VEXAS within a cohort of patients with RP have not been defined. We undertook this study to define the prevalence of somatic mutations inUBA1 in patients with RP and to create an algorithm to identify patients with genetically confirmed VEXAS among those with RP.MethodsExome and targeted sequencing ofUBA1 was performe...
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: Original Article Source Type: research
ConclusionOur data from early 2021 indicate that a large proportion of Swedish SLE patients had serological signs of exposure to SARS-CoV-2 but apparently with a minor impact on the SLE course. Use of steroids and hydroxychloroquine showed no distinct effects, and self-reported COVID-19-related symptoms correlated poorly with all antibody isotypes.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Rheumatoid arthritis (RA) is associated with an increased risk of venous thromboembolism (VTE) occurrence. In this work, we assessed the incidence and predictive factors of VTE in our “real-life” cohort of RA patients. To contextualize our results, we reviewed the available literature about this topic. We performed a retrospective analysis of prospectively followed-up patients with RA attending our Rheumatologic Clinic between January 2010 and December 2020. Each patient was investigated for VTE occurrence. Incident cases were reported as incidence proportion and incidence rate per 1000 person-years at risk....
Source: Medicine - Category: Internal Medicine Tags: Research Article: Observational Study Source Type: research
J Rheumatol. 2021 Jun 15:jrheum.210131. doi: 10.3899/jrheum.210131. Online ahead of print.ABSTRACTIn the postgenomic era, the genomic revolution in translational medicine has not escaped the attention of clinicians and researchers focusing on the medical management of venous thromboembolism (VTE). VTE, a multifactorial disease, is a worldwide health problem affecting people of all ages, sexes, and races, and has 2 major subtypes: deep vein thrombosis and pulmonary embolism.1.PMID:34329186 | DOI:10.3899/jrheum.210131
Source: Journal of Rheumatology - Category: Rheumatology Authors: Source Type: research
FRIDAY, July 23, 2021 -- For patients with rheumatoid arthritis (RA), there are common risk factors for venous thromboembolism (VTE) and atherosclerotic cardiovascular disease (ASCVD), and the risk for ASCVD is increased after unprovoked VTE,...
Source: Drugs.com - Pharma News - Category: Pharmaceuticals Source Type: news
CONCLUSION: Autoantibodies appear to increase CVD risk; however, the magnitude of the increase and the types of CVD outcomes affected are still unclear. Prospective studies with larger populations are required to further understand and quantify the association, including the causal pathway, between specific risk factors and CVD outcomes in RA patients.PMID:34262386 | PMC:PMC8246480 | DOI:10.1177/11795441211028751
Source: Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders - Category: Orthopaedics Authors: Source Type: research
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